Monoclonal antibodies against T cell surface markers have been used experimentally in vivo in an attempt to delete T cells and allow for subsequent tolerance to foreign transplantation antigens. One such monoclonal antibody OKT3, directed against the CD3 delta chain of human T cell receptor complex has been shown to have profound immunosuppressive effects on transplantation rejection responses in vivo. We have developed a hamster monoclonal (145-2C11) directed against the CD3 epsilon chain of the murine T cell receptor complex. Like its anti human CD3 counterpart, it can significantly effect transplantation responses in vivo. Animals treated with small quantities of the anti-T3 antibody exhibit prolonged skin graft rejection by as much as three weeks. In addition, cells removed from anti-T3 treated mice are unresponsive to a variety of alloantigens including both class I and class II. Future studies will be designed to examine the role of in vivo treatment with anti T3 on bone marrow engraftment and abrogation of GVH and HVG responses.